Focused droplet nebulizer for evaporative light scattering detector

ABSTRACT

A focused droplet nebulizer of the invention produces substantially uniform droplets of a predetermined size. Droplets are pushed out through a small outlet orifice by the contraction of a chamber. The droplets can be carried on a substantially non-divergent path in a drift tube. A piezo membrane micro pump acts in response to an electrical control signal to force a droplet out of the outlet orifice. The nebulizer can operate at frequencies permitting a stream of individual droplets of the predetermined size to be sent along the substantially non-divergent path in the drift tube in a preferred embodiment ELSD device.

FIELD OF THE INVENTION

The invention is in the field of evaporative light scattering detection.

BACKGROUND

Evaporative light scattering detectors (ELSDs) are used routinely forLiquid Chromatography (LC) analysis. In an ELSD, a liquid sample isconverted to droplets by a nebulizer. As the droplets traverse a drifttube, the solvent portion of the droplets evaporates, leaving lessvolatile analyte. The sample passes to a detection cell, where lightscattering of the sample is measured. ELSDs can be used for analyzing awide variety of samples.

The present inventors identify the nebulizer as a limit on theeffectiveness of the detection capabilities of ELSDs. One problem withconventional nebulizers is that complete solvent evaporation does notoccur in the drift tube. The expanding trajectory and variable sizes ofthe droplets produced by conventional nebulizers contributes to theincomplete evaporation and erratic measurement performance. Dropletsenter the detection cell and cause scattering that is detected. Thescatter effect of droplets is indicated in conventional ELSDs by thefact that substantial scattering is detected in the absence of analytes.This droplet scattering creates a large level of background noise.Accordingly, with typical ELSDs, it is only possible to measuredifferential scattering, where scattering from the analyte is muchgreater than that from incompletely volatilized solvent droplets.

Droplets that are too small to carry sufficient analyte are alsoproduced within the distribution of droplets produced by a conventionalnebulizer. The small droplets result in analyte particles that are toosmall to contribute to the detection signal. However, the small dropletsincrease solvent vapor pressure in the drift tube. Higher vapor pressureretards evaporation in the drift tube. Incomplete evaporation leads tothe background noise from scattering caused by droplets as discussedabove.

If the droplet size distributions and evaporation rate were constant inthe conventional ELSD nebulizers, then the resultant background noisecould, to a certain degree, be accounted for in the measurement.However, the rate of incomplete droplet vaporization and theirdistribution (size and number) tends to change randomly with time. Thiscauses uncertainty in the analyte signal, in addition to the substantiallevel of background noise.

One conventional strategy for addressing the droplet distributionproblem of conventional nebulizers is to remove larger droplets. Animpactor has been used in the drift tube of conventional ELSDs tointercept large droplets, which are collected and exit the drift tubethrough an outlet drain. Additional condensation collects on the wallsof the drift tube due to the divergence of spray from the nebulizer, andalso drains from the outlet drain. A percentage of the divergent spraythat exits via the outlet drain includes properly sized droplets withanalyte. Excluding larger droplets produced by a conventional nebulizerproves difficult in practice because the nature of the dropletdistribution depends strongly on three factors: mobile phasecomposition, mobile phase flow rate and carrier gas flow rate. Thedependence is highly interactive, which makes the spray hard to controland difficult to model. These undesirable nebulizer characteristicsplace extraordinary demands on the structural design of ELSD units,making their design very complicated and highly empirical.

SUMMARY OF THE INVENTION

A focused droplet nebulizer of the invention produces substantiallyuniform droplets of a predetermined size. Droplets are pushed outthrough a small outlet orifice by the contraction of a chamber. Thedroplets can be carried on a substantially non-divergent path in a drifttube. A piezo membrane micro pump acts in response to an electricalcontrol signal to force a droplet out of the outlet orifice. Thenebulizer can operate at frequencies permitting a stream of individualdroplets of the predetermined size to be sent along the substantiallynon-divergent path in the drift tube of a preferred embodiment ELSDdevice.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 illustrates an evaporative light scattering detector (ELSD)including a focused droplet nebulizer in accordance with a preferredembodiment of the invention;

FIG. 2 illustrates the focused droplet nebulizer of FIG. 1;

FIGS. 3A and 3B illustrate a piezo membrane micro pump of the nebulizerof FIGS. 1 and 2;

FIG. 4 illustrates a structure for reduced flow sampling of effluent inaccordance with an embodiment of the invention;

FIG. 5 illustrates a structure for reduced flow sampling of effluent inaccordance with another embodiment of the invention;

FIG. 6 illustrates a structure for reduced flow sampling of effluent inaccordance with another embodiment of the invention; and

FIGS. 7A and 7B illustrate an optical detection cell of the ELSD of FIG.1.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The problems inherent with the use of a conventional nebulizerultimately limit performance in evaporative light scattering detectors(ELSDs). Size, complexity, and cost are also adversely affected by thenebulizer. The invention provides a focused droplet nebulizer. Anebulizer of the invention produces substantially uniform sizeddroplets. Preferred embodiment nebulizers also provide a preciselycontrolled droplet production rate and deliver droplets along a focusedpath. An ELSD of the invention uses a focused droplet nebulizer toreduce background noise and improve the state of ELSD detection.

A preferred embodiment focused droplet nebulizer includes a piezomembrane micro pump. The piezo membrane micro pump has an inlet with acheck valve that allows liquid to flow one way into the pump. When thepiezo membrane expands, liquid is drawn into the pump and when the piezomembrane contracts, liquid is forced out a tiny outlet orifice. Thiscreates a small single droplet. The check valve ensures that littleliquid flows back through the inlet port. The droplet output is strictlycontrolled by an electrical signal. In other embodiments, a plurality oforifices and/or piezo membrane elements are used to produce paralleldroplet streams.

Dimensions of the focused droplet nebulizer are set to produce dropletsof a predetermined size. Dimensions may be set, for example, to producedroplets anywhere within in the approximate range of between 10 and 100μm, which are sizes typically of interest in ELSD systems. Droplets in aparticular physical embodiment constructed in accordance with theinvention have a very narrow size distribution, typically 5% standarddeviation. Applied to an ELSD, substantially all droplets willcontribute to the detection signal. The rate of droplet production iscontrolled independently by electrical signal, e.g. a periodic signal,fed to the micro pump. Thus, the rate of droplet formation can be easilyvaried so as to optimize the signal to noise ratio. The droplet size isindependent of droplet production rate and is not strongly dependent onliquid composition. There is substantially no divergence in the dropletpath, typically 1-2 degrees standard deviation. Operation can beindependent of the flow rate of the carrier gas. Piezo element micropumps have a relatively low cost, tolerate a wide range of organic andaqueous liquids, and have a relatively long lifetime.

Preferred embodiments of the invention will now be discussed withreference to the drawings. The particular exemplary devices will be usedfor purposes of illustration of the invention, but the invention is notlimited to the the particular illustrated devices.

FIG. 1 illustrates a preferred embodiment ELSD including a focuseddroplet nebulizer. A liquid chromatography (LC) column 100 provideseffluent 102 (a.k.a. the mobile phase) to the focused droplet nebulizer104. The focused droplet nebulizer also is provided with carrier gas106. A controller 107 controls the droplet production of the focuseddroplet nebulizer 104. Under control of signals from the controller 107,the nebulizer 104 produces droplets of a predetermined size that dependsupon the physical characteristics of a piezo membrane micro pump in thefocused droplet nebulizer. For example, droplets in the approximaterange of between 10 and 100 μm, which are of interest to ELSD systems,are readily produced by a piezo membrane micro pump.

The focused droplet nebulizer 104, under control of the controller 107,produces substantially uniformly sized droplets, e.g., droplets having avery narrow size distribution, typically 5% standard deviation. The rateof droplet production is controlled readily by an electrical signal,e.g., a periodic signal, provided to the micro pump by the controller107. The rate of droplet formation can be varied by the controller 107to optimize the signal to noise ratio. This can be an automaticoptimization provided by the controller 107, or can be an optimizationconducted with operator input to the controller 107. Droplet size isindependent of droplet production rate and is substantially independentof liquid composition.

The focused droplet nebulizer 104 sends the uniformed sized droplets ona substantially non-divergent focused path, typically 1-2 degreesstandard deviation, into the flow of carrier gas down a drift tube 108,which is a heated section of tubing through which gas/droplets flow, andin which evaporation occurs. The mobile phase (solvent) tends toevaporate as the droplet stream passes along drift tube 108. The gasstream enters an optical cell 110, which is the detection module of theunit. The stream passes through the cell 110 and out an exit port 112 asa waste gas steam 114.

The basis of the detection method is the amount of light scatteredwithin the detection cell 110. Ideally, scattering will arise only fromsubstances (analytes) dissolved in the mobile phase and scattering fromthe mobile phase per se will be negligible. In the ideal case, allmobile phase molecules will be converted to gas in the drift tube 108,and will produce little or no scattering in the optical cell 110.Analytes, if present, will not vaporize but will be left as airborneparticles, which produce substantial light scattering as they passthrough the optical cell 110. Thus, if the mobile phase 102 contains ananalyte, light scattering will be observed within the cell 110, whereasif the mobile phase 102 contains no analyte, little or no lightscattering will be observed within the cell 110. With this situation,whenever an analyte exits the LC column, an analyte peak (strongscattering by particles) will be observed above the baseline (weakscattering by solvent).

Evaporation is highly efficient in the ELSD of FIG. 1, as the focuseddroplet nebulizer 104 produces substantially uniform sized dropletsalong a substantially non-divergent path. The problems of conventionalnebulizers that include droplet size distributions and divergent spraysare avoided and background noise in the detection signal issubstantially reduced. The conventional nebulizers include a spraynozzle that produces a large number of too small and too large dropletson a divergent spray. The particles that are too small do not contributeto the signal; however, they increase the solvent vapor pressure, whichdecreases the efficiency of the drift tube by retarding solventevaporation. The large droplets tend to undergo incomplete vaporizationand their distribution (size and number) changes randomly with time.Thus, they produce baseline noise in the absence of analyte as well asuncertainty in the analyte signal itself. The ELSD of FIG. 1 solves suchproblems.

FIG. 2 shows the focused droplet nebulizer 104 of FIG. 1. The focuseddroplet nebulizer makes use of a piezo membrane micro pump 202. Piezomembrane (aka diaphragm) micro pumps use, for example, a piezo-ceramicelement as the diaphragm/membrane. Piezo membrane micro pumps areavailable from a number of commercial sources.

Within the focused droplet nebulizer 104, the piezo membrane micro pump202 receives the mobile phase 102. The mobile phase 102 enters the micropump 202, which is centrally mounted in a gas manifold 204. Carrier gas206 enters the manifold 204 and exits into the drift tube 108 in aconcentric manner around the micro pump 202. The gas manifold gives auniform flow of gas to carry the droplets into the drift tube 108.Substantially uniform droplets 210 are produced by the micro pump 202 ata size determined by the micro pump outlet orifice and at a ratedetermined by the frequency of the signal applied to the micro pumppiezo by the controller 107. The droplet path is substantiallynon-divergent and unidirectional as shown and is carried along by thecarrier gas stream 208.

FIGS. 3A and 3B illustrate additional details and operation of the micropump 202 of the nebulizer 104. The micro pump 202 has a body 302 thatdefines a chamber 303. Each of an inlet 304 and outlet orifice 306includes a check valve 308. A piezo membrane/diaphragm 310 is anintegral part of the chamber body 302. FIG. 3A illustrates a liquidintake action. An electrical signal (pulse) is sent to the piezomembrane 310 from the controller 107, causing it to move such that thechamber volume is increased and liquid is pulled into the chamber bodythrough the inlet 304. The check valve 308 on the outlet orifice 306eliminates flow into the chamber through the outlet orifice 306. FIG. 3Billustrates droplet formation and expulsion, which occurs when the piezomembrane 310 moves such that the chamber volume is decreased and liquidis forced through the outlet orifice 306 in the form of a droplet. Thecheck valve 308 on the inlet 304 eliminates liquid flow back through theinlet 304. The rate of droplet formation is controlled by the pulsingrate, up to about 5 kHz. Each pulse results in one droplet beingexpelled by the pump for “drop on demand” operation. The substantiallyuniform predetermined droplet size is controlled by the size of thechamber 303 and the diameter of the outlet orifice 306.

Due to the substantially consistent drop size and substantiallynon-divergent path, the ELSD of FIG. 1 will have a noise reductionbecause large droplets of conventional devices are eliminated. The ELSDwill also have a higher detection signal because the droplets areuniformly sized and propagate on a path wherein substantially all of thedroplets make a contribution to the detection signal. Lower carrier gasrates are required. The focused droplet nebulizer 104 also has a reducedsize compared to typical conventional nebulizers. Since evaporation ismore efficient, the internal size of the drift tube 108 can be decreasedand the drift tube can be operated at lower temperatures than used incurrent typical commercial devices. Lower temperature operation canminimize signal loss for analytes that tend to partially vaporize, oftenreferred to as semi-volatiles.

In the ELSD of FIG. 1, the focused droplet nebulizer 104 receiveseffluent from the LC column 100 at a lower rate than is used inconventional nebulizers. A typical conventional commercial nebulizeraccepts a range of mobile phase flow rates and delivers a droplet sprayconsistent with the experimental liquid flow rate, which may be as highas 5 mL/min. However, the focused droplet nebulizer 104 of the inventionuses a piezo membrane micro pump that delivers a fixed flow rate ofdroplets depending on the predetermined droplet size of the nebulizer104 and the frequency of the control signal applied by the controller.

For example, a 100 picoliter (pL) droplet with an 8 kHz signal wouldrequire a liquid input flow rate of about 0.05 mL/min, which is muchsmaller than typical LC liquid flow rates used in a conventional ELSDdevice. Assuming an unmodified typical LC column 100, only a fraction ofthe column effluent will be used by the focused droplet nebulizer 104.Sampling the mobile phase effluent can be conducted in a manner thatrepresents the actual composition of the effluent at every instant, andwithout requiring that the entire volume of effluent pass through themicro pump. Thus, the focused droplet nebulizer 104 can be used with atypical conventional LC column 100 with appropriate sampling, or amodified, lower rate LC column can be used.

Sampling of the effluent for reduced flow into the focused dropletnebulizer 104 can be achieved by various techniques. A structure forreduced flow sampling is shown in FIG. 4. In FIG. 4, effluent 102 ispassed through a tee 402, with the focused droplet nebulizer 104attached to relatively short tube 406 of the tee 402. The focuseddroplet nebulizer 104 sends liquid through its micro pump's outletorifice 306 to the ELSD drift tube 108 (not shown in FIG. 4). Anothertube 408 of the tee 402, is substantially wider and accepts the mainportion of the effluent 102. The tube 406 is also relatively short tokeep backpressure relatively low and permit the piezo membrane micropump in the focused droplet nebulizer 104 to draw as much liquid as isrequired from the tee 402. The relative diameters of the tubes 406 and408 are set to accommodate the flow limit of the focused dropletnebulizer 104.

Another structure for reduced flow sampling is shown in FIG. 5. The FIG.5 structure can handle larger flows than the FIG. 4 structure. Thefocused droplet nebulizer 104 is attached to a very small diametersampling tube 502, which is in turn mounted so that it penetrates intothe interior of a tube 504 that carries the effluent 102. The focuseddroplet nebulizer 104 draws as much liquid as is required and providesfocused droplet output through its outlet orifice 306.

Another structure for reduced flow sampling is shown in FIG. 6. A smalldiameter sampling tube 602 is attached to a main flow tube 604 carryingthe effluent 102. A flow controller 606 delivers a small volume ofliquid to a tee 608. The focused droplet nebulizer 104 is attached toone tube of the tee 608 and excess liquid flows out a waste tube 610.The flow controller 606 ensures that the focused droplet nebulizer 104does not experience intolerable back pressure.

Analyte enters the optical cell 110 after traversing the drift tube 108.The optical cell is shown in FIGS. 7A and 7B. As seen in top view (FIG.7A), a light source 702 produces a light beam 704 that travels throughthe cell 110 and enters a light trap 706, which minimizes stray lightthat can interfere with detection of the scattering due to analyte. Agas stream 708 flows through the cell 110 as shown, normal to the lightbeam 704. In the side view (FIG. 7B) the light beam 704, not shown, isperpendicular to the plane of the paper. Thus, the gas stream 708 in thecell 110 encounters the light beam near the center of the cell 110,within a cross section 710. Analyte particles scatter light and aportion of the scattered light 712 is refocused by a lens 714, so thatthe refocused light 716 strikes an optical detector 718. This detectedlight is measured and forms the basis for quantitation in the analysis.

While specific embodiments of the present invention have been shown anddescribed, it should be understood that other modifications,substitutions and alternatives are apparent to one of ordinary skill inthe art. Such modifications, substitutions and alternatives can be madewithout departing from the spirit and scope of the invention, whichshould be determined from the appended claims.

Various features of the invention are set forth in the appended claims.

1. A focused droplet nebulizer for connecting with a drift tube in anevaporative light scattering detector, the nebulizer comprising: a gasmanifold having an output for releasing a flow of carrier gas into thedrift tube; a piezo membrane micro pump mounted in the gas manifold,said micro pump comprising: a piezo membrane responsive to an electricalcontrol signal; an effluent input to accept liquid effluent uponexpansion movement of said piezo membrane; and a droplet outlet orificeto expel a single liquid effluent droplet of a predetermined size uponeach opposite movement of said piezo membrane into the drift tube; andwherein the flow of carrier gas in the drift tube receives each singleliquid effluent droplet expelled into the drift tube from said dropletoutlet orifice and carries the received droplets in a substantiallynon-divergent path through the drift tube.
 2. The nebulizer of claim 1,wherein said carrier gas is directed in a concentric manner about saiddroplet outlet orifice.
 3. The nebulizer of claim 1, wherein saiddroplet outlet orifice is sized such that the predetermined size of saidsingle liquid effluent droplet is in the range of 10 and 100 μm.
 4. Anevaporative light scattering detector, comprising: a nebulizer accordingto claim 1 including one or more droplet outlet orifices, an effluentsupply to said effluent input; a drift tube accepting the carrier gasand each single liquid effluent droplet expelled from said dropletoutlet orifice; an optical detection cell; and a controller to supplythe electrical control signal at a predetermined frequency, wherein thepredetermined frequency controls a rate at which each single liquideffluent droplet is expelled from the droplet outlet orifice of thepiezo membrane micro pump.
 5. The detector of claim 4, wherein saideffluent supply comprises a liquid chromatography column.
 6. Thedetector of claim 4, further comprising flow sampling means for reducingflow of liquid effluent from said liquid chromatography column to thenebulizer.
 7. A focused droplet nebulizer for connecting with a drifttube in an evaporative light scattering detector, the nebulizercomprising: a gas manifold having an output for releasing a flow ofcarrier gas into the drift tube; and a piezo membrane micro pumpcontrolled by an electrical control signal, said piezo membrane micropump comprising: a liquid effluent chamber; an inlet that accepts liquideffluent into the liquid effluent chamber in response to expanding ofsaid liquid effluent chamber; and at least one droplet outlet orifice,each at least one droplet outlet orifice adapted to produce a singledroplet of liquid effluent from the liquid effluent chamber in responseto a contracting of said liquid effluent chamber independent of the flowof carrier gas and to expel the single droplet of liquid effluent intothe flow of carrier gas, wherein the expelled droplets are carried bythe flow of carrier gas in a substantially non-divergent path throughthe drift tube.
 8. The nebulizer of claim 7, further comprising: a drifttube for accepting droplets of liquid effluent expelled from said atleast one droplet outlet orifice.
 9. The nebulizer of claim 7, whereinsaid at least one droplet outlet orifice and said chamber are sized toproduce droplets of liquid effluent of a predetermined size in the rangeof 10 to 100 μm.
 10. An evaporative light scattering detector,comprising: an optical detection cell; a drift tube through which astream of liquid effluent droplets are delivered to the opticaldetection cell; a focused droplet nebulizer for producing the stream ofliquid effluent droplets, said nebulizer comprising: a gas manifoldhaving an output for releasing a flow of carrier gas into the drifttube; a piezo membrane micro pump mounted in the gas manifold, saidmicro pump comprising: a piezo membrane responsive to an electricalcontrol signal; an effluent input for receiving liquid effluent from aneffluent supply upon expansion movement of the piezo membrane; and adroplet outlet orifice for expelling the stream of liquid effluentdroplets into the drift tube, said droplet orifice outlet expelling asingle effluent droplet of a predetermined size upon each oppositemovement of the piezo membrane, said drift tube receiving the carriergas and each single liquid effluent droplet expelled from the dropletoutlet orifice, wherein the stream of liquid effluent droplets comprisesa plurality of single effluent droplets of substantially uniform sizeand is carried by the flow of carrier gas in a substantiallynon-divergent path through the drift tube; and a controller to supplythe electrical control signal to the piezo membrane of the micro pump ata predetermined frequency, wherein the predetermined frequency controlsa rate at which each single liquid effluent droplet is expelled from thedroplet outlet orifice of the micro pump.